Contribution of maternal oxygenic state to the effects of chronic postnatal hypoxia on mouse body and brain development

Abstract

1–2% of live births are to very low birth weight, premature infants that often show a developmental trajectory plagued with neurological sequelae including ventriculomegaly and significant decreases in cortical volume. We are able to recapitulate these sequelae using a mouse model of hypoxia where early postnatal pups are exposed to chronic hypoxia for one week. However, because the timing of hypoxic exposure is so early in development, dams and pups are housed together in the hypoxic chamber, and therefore dams are also subjected to the same hypoxic conditions as the pups. To understand the relative contribution of hypoxia directly on the pups as opposed to the indirect contribution mediated by the effects of hypoxia and potential alterations in the dam’s care of the pups, we examined whether reducing the dams exposure to hypoxia may significantly increase pup outcomes on measures that we have found consistently changed immediately following chronic hypoxia exposure. To achieve this, we rotated dams between normoxic and hypoxic conditions, leaving the litters untouched in their respective conditions and compared gross anatomical measures of normoxic and hypoxic pups with non-rotating or rotating mothers. As we expected, hypoxic-rearing decreased pup body weight, brain weight and cortical volume. Reducing the dam’s exposure to hypoxic conditions actually amplified the effects of hypoxia on body weight, such that hypoxic pups with rotating mothers showed significantly less growth. Interestingly, rotation of hypoxic mothers did not have the same deleterious effect on brain weight, suggesting the presence of compensatory mechanisms conserving brain weight and development even under extremely low body weight conditions. The factors that potentially contribute to these compensatory changes remain to be determined, however, nutrition, pup feeding/metabolism, or changes in maternal care are important candidates, acting either together or independently to change pup body and brain development.

Impaired Interneuron Development in a Novel Model of Neonatal Brain Injury

“…After delivery, dams and litters were housed in 10.9% oxygen from P3 to P10 to produce CSH, with control litters housed in the same room outside of the hypoxia chamber. No adverse effects of hypoxia were noted on dams or pups, except for mild growth restriction that resolved over the first postnatal month (Salmaso et al, 2015). Four experimental groups were studied: mice treated with saline and reared under normoxia (MIA–/CSH–), mice subjected to MIA and reared under normoxia (MIA+/CSH–), mice treated with saline and reared under CSH (MIA–/CSH+), and mice subjected to MIA and reared under CSH (MIA+/CSH+).…”

Correlation between preconception maternal non-occupational exposure to interior decoration or oil paint odour and average birth weight of neonates: findings from a nationwide cohort study in China’s rural areas

“…These solvents may induce hypoxia, fetal malnutrition and ultimately other adverse pregnancy outcomes. 18 However, anoxia is always held responsible for LBW or SGA, 19 but it does not increase the baby’s birth weight or the risk of macrosomia, which points to other mechanisms to explain the correlation between maternal exposure to decoration pollutants and fetal growth.…”

Translatomic database of cortical astroglia across male and female mouse development reveals two distinct developmental phenotypes

“…All immunohistochemical processes took place at room temperature (∼21 °C) as per our previous studies 25,60,64 . One representative slide was taken from every subject and all subjects were processed simultaneously.…”